Structural information on nanometer-sized gold particles has been limited, due in part to the problem of preparing homogeneous material. Here we report the crystallization and x-ray structure determination of a p-mercaptobenzoic acid (p-MBA)-protected gold nanoparticle, which comprises 102 gold atoms and 44 p-MBAs. The central gold atoms are packed in a Marks decahedron, surrounded by additional layers of gold atoms in unanticipated geometries. The p-MBAs interact not only with the gold but also with one another, forming a rigid surface layer. The particles are chiral, with the two enantiomers alternating in the crystal lattice. The discrete nature of the particle may be explained by the closing of a 58-electron shell.

Synthesis, characterization, and functionalization of self-assembled, ligand-stabilized gold nanoparticles are long-standing issues in the chemistry of nanomaterials. Factors driving the thermodynamic stability of well documented discrete sizes are largely unknown. Herein, we provide a unified view of principles that underlie the stability of particles protected by thiolate (SR) or phosphine and halide (PR 3, X) ligands. The picture has emerged from analysis of large-scale density functional theory calculations of structurally characterized compounds, namely Au 102(SR)44, Au39(PR3)14X6 ؊ , Au 11(PR3)7X3, and Au13(PR3)10X2 3؉ , where X is either a halogen or a thiolate. Attributable to a compact, symmetric core and complete steric protection, each compound has a filled spherical electronic shell and a major energy gap to unoccupied states. Consequently, the exceptional stability is best described by a ''noble-gas superatom'' analogy. The explanatory power of this concept is shown by its application to many monomeric and oligomeric compounds of precisely known composition and structure, and its predictive power is indicated through suggestions offered for a series of anomalously stable cluster compositions which are still awaiting a precise structure determination.density functional theory ͉ monolayer-protected cluster

The inherent complexity of cellular signaling networks and their importance to a wide range of cellular functions necessitates the development of modeling methods that can be applied toward making predictions and highlighting the appropriate experiments to test our understanding of how these systems are designed and function. We use methods of statistical mechanics to extract useful predictions for complex cellular signaling networks. A key difficulty with signaling models is that, while significant effort is being made to experimentally measure the rate constants for individual steps in these networks, many of the parameters required to describe their behavior remain unknown or at best represent estimates. To establish the usefulness of our approach, we have applied our methods toward modeling the nerve growth factor (NGF)-induced differentiation of neuronal cells. In particular, we study the actions of NGF and mitogenic epidermal growth factor (EGF) in rat pheochromocytoma (PC12) cells. Through a network of intermediate signaling proteins, each of these growth factors stimulates extracellular regulated kinase (Erk) phosphorylation with distinct dynamical profiles. Using our modeling approach, we are able to predict the influence of specific signaling modules in determining the integrated cellular response to the two growth factors. Our methods also raise some interesting insights into the design and possible evolution of cellular systems, highlighting an inherent property of these systems that we call 'sloppiness.'

Previous X-ray crystal structures have given insight into the mechanism of transcription and the role of general transcription factors in the initiation of the process. A previous structure at 4.5 Å resolution of an RNA polymerase II-general transcription factor TFIIB complex revealed the N-terminal region of TFIIB, including a loop termed the "B-finger" reaching into the active center of the polymerase where it may interact with both DNA and RNA, but this structure showed little of the C-terminal region. A new crystal structure of the same complex at 3.8 Å resolution obtained under different solution conditions is complementary with the previous one, revealing the C-terminal region of TFIIB, located above the polymerase active center cleft, but showing none of the B-finger. In the new structure, the linker between the N-and C-terminal regions can also be seen, snaking down from above the cleft towards the active center. The two structures, taken together with others previously obtained, dispel longstanding mysteries of the transcription initiation process.Cellular RNA polymerases require protein cofactors for promoter recognition and the initiation of transcription. In bacteria, this requirement is met by a single protein, the sigma factor (1). By contrast, RNA polymerase II (pol II) of eukaryotes depends on five "general" factors, comprising some 30 polypeptides, for promoter-dependent transcription. The general factors, known as TFIIB, -D, -E, -F, and -H, assemble with the polymerase and promoter DNA in a complex of approximately 2 MDa at every round of the initiation of transcription. Promoters containing a TATA box may be transcribed with only the TATA-binding protein (TBP) subunit of TFIID, whereas TATA-less promoters require the TBP-associated factor (TAF) subunits of TFIID as well. TFIIB and TBP/TFIID are primarily responsible for promoter recognition; indeed, TFIIB and TBP are alone sufficient for pol II transcription of a negatively supercoiled promoter in vitro (2). In the absence of supercoiling, TFIIE and TFIIH are required to introduce negative superhelical strain and unwind promoter DNA for the initiation of transcription. Structural studies of pol II, both alone and as an actively transcribing complex, have revealed a large conformational change between the "closed" complex containing entirely double stranded promoter DNA and the "open" complex containing an unwound region ("transcription bubble"). The promoter DNA is straight in the closed complex, but in the open complex it bends about 90° and descends some 30 A into the central polymerase cleft. The mechanism of this large conformational change has remained unclear. The general factors are believed to assist and to remain associated throughout the process, but following initiation, they are released and the polymerase escapes from the promoter. The challenge is to understand how protein-protein interactions can be formed during the assembly of the transcription initiation complex and then reversed during promoter escape.Biochemical and...

The 7-methyl guanosine cap structure of RNA is essential for key aspects of RNA processing, including pre-mRNA splicing, 3' end formation, U snRNA transport, nonsense-mediated decay and translation. Two cap-binding proteins mediate these effects: cytosolic eIF-4E and nuclear cap-binding protein complex (CBC). The latter consists of a CBP20 subunit, which binds the cap, and a CBP80 subunit, which ensures high-affinity cap binding. Here we report the 2.1 A resolution structure of human CBC with the cap analog m7GpppG, as well as the structure of unliganded CBC. Comparisons between these structures indicate that the cap induces substantial conformational changes within the N-terminal loop of CBP20, enabling Tyr 20 to join Tyr 43 in pi-pi stacking interactions with the methylated guanosine base. CBP80 stabilizes the movement of the N-terminal loop of CBP20 and locks the CBC into a high affinity cap-binding state. The structure for the CBC bound to m7GpppG highlights interesting similarities and differences between CBC and eIF-4E, and provides insights into the regulatory mechanisms used by growth factors and other extracellular stimuli to influence the cap-binding state of the CBC.